Original Article

Neuropsychopharmacology (2008) 33, 1071–1083; doi:10.1038/sj.npp.1301496; published online 4 July 2007

Aniracetam Reversed Learning and Memory Deficits Following Prenatal Ethanol Exposure by Modulating Functions of Synaptic AMPA Receptors

Julia Vaglenova1, Noemi Pandiella1, Nayana Wijayawardhane1, Tiru Vaithianathan1, Sandjay Birru1, Charles Breese1, Vishnu Suppiramaniam1 and Clark Randal1

1Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA

Correspondence: Dr J Vaglenova, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. Tel: +1 334 844 83 67; Fax: +1 334 844 8331; E-mail: vagleju@auburn.edu

Received 6 December 2006; Revised 21 May 2007; Accepted 29 May 2007; Published online 4 July 2007.

Top

Abstract

Specific pharmacological treatments are currently not available to address problems resulting from fetal ethanol exposure, described as Fetal Alcohol Syndrome or Fetal Alcohol Spectrum Disorders (FASD). The present study evaluated the therapeutic effects of aniracetam against cognitive deficits in a well-characterized and sensitive FASD Sprague–Dawley rat model. Ethanol, administered orally at a moderate dose (4g/kg/24h; 38% v/v) during the entire course of pregnancy, caused severe cognitive deficits in offspring. Furthermore, both progeny genders were affected by a spectrum of behavioral abnormalities, such as a delay in the development of the righting reflex, poor novelty seeking behavior, and high anxiety levels in female rats. Cognitive disabilities, monitored in adult rats by a two-way active avoidance task, correlated well with a significant reduction of AMPA (α-amino-3 hydro-5 methyl-isoxazole propionic acid) receptor-mediated miniature excitatory postsynaptic responses (mEPSCs) in the hippocampus. Administration of aniracetam for 10 days (post-natal days (PND) 18–27), at a dose of 50mg/kg reversed cognitive deficits in both rat genders, indicated by a significant increase in the number of avoidances and the number of ‘good learners’. After the termination of the nootropic treatment, a significant increase in both amplitude and frequency of AMPA receptor-mediated mEPSCs in hippocampal CA-1 pyramidal cells was observed. Significant anxiolytic effects on PND 40 also preceded acquisition improvements in the avoidance task. This study provides evidence for the therapeutic potential of aniracetam in reversing cognitive deficits associated with FASD through positive post-natal modulation of AMPA receptors.

Keywords:

prenatal ethanol, learning and memory, avoidance, anxiety, AMPA receptors, aniracetam

Top

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated

Extra navigation

.
ADVERTISEMENT